He and his Deputy Nick Clegg are to go head to head over the Alternative Vote and Britain’s voting system.
It is the first time since the coalition came into force that the two leaders have publicly held different opinions over policy.
Earlier this week Colin Firth and Helena Bonham Carter lent their support to the “Yes to AV” campaign.
Conservative leader Cameron is expected to say that AV is “the precise opposite of what we need right now” and highlight that if AV had been used in the election last May, former Labour Prime minister Gordon Brown would still be in power.
Cameron is not expected to attack Clegg or the Lib-Dems in his rhetoric but focus on the drawbacks of AV such as the possibility of the third-placed party winning and the fact than the system is only used by three nations around the world – Australia, Fiji and Papua New Guinea.
The official “No to AV” campaign group however is set to make Clegg the centre point of its campaign against AV.
The Lib-Dem leader will argue that the current voting system is “out of date” makes MPs complacent and lazy and is the cause of distrust in politicians and the Government.
He will also say that AV will “be good for our democracy” and mean the end of wasted votes in so called “safe seats”.
The Bill was eventually passed by Parliament earlier this week following delays caused by opposition in the House of Lords. A referendum will be held on 5 May when the public will get to vote whether to reform the UK’s voting system by bringing in AV or retain the existing first pas the post method.